The present study was to investigate the effects of water extracts of $Acanthopanax$ $divaricatus$ $var.$ $albeofructus$ stem extract (ADE) on an exacerbated immune function through utilization of a protein-energy malnutrition (PEM) diet. ADE has been used in Korea as a tonic and sedative agents as well as a drug with ginseng like activities. However, there is no pronouncing about the immune system on the PEM feeding mice. The immobility time were significantly decreased in the ADE-administrated group as compared to the control group on the forced swimming test ($P$ <0.05). The level of aspartate aminotransferase and lactate dehydrogenase in blood was significantly reduced in the ADE-administrated group ($P$ <0.05). ADE also significantly decreased production of interferon- ${gamma}$ and interleukin (IL)-4 but not IL-2 in splenocytes ($P$ <0.05). We used a manually antibody microarray to carry out the signaling protein microarray analysis. Unfortunately, we did not find change of protein expression. These results suggest that ADE have the anti-fatigue effect and the immune regulation effect.